Objective To systematically analyze the spatiotemporal distribution characteristics and epidemiological trends of tracheal, bronchus, and lung cancer (TBL) disease burden attributed to air pollution globally and in China and the United States from 1990 to 2021, and to assess the patterns of disease burden changes from 2022 to 2031 based on predictive models, providing a scientific basis for formulating targeted TBL prevention and control strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we analyzed the disease burden data of TBL attributed to air pollution globally and in China and the United States from 1990 to 2021. R Studio 4.3.2 software was used to analyze the corresponding trends and the Bayesian age-period-cohort (BAPC) prediction model was used to predict the status of the disease burden of TBL attributed to air pollution in the world and in China and the United States from 2022 to 2031. Results In 2021, China had the highest number of deaths and disability-adjusted life years attributed to air pollution (211 400 patients and 4.8947 million person-years), followed by the United States (6 000 patients and 124 300 person-years). The age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) of TBL due to air pollution in the world and in China and the United States showed a decreasing trend. From 1990 to 2021, the ASMR and ASDR of TBL in China due to air pollution were much higher than those in the United States and the global average. In terms of gender, from 1990 to 2021, the disease burden of male patients with TBL attributed to air pollution was much higher than that of female patients. The BAPC prediction model showed that from 2022 to 2031, the ASMR and ASDR of TBL attributed to air pollution showed an upward trend globally, while they showed a downward trend in China and the United States. Conclusion Over the past 30 years, the air pollution-related TBL disease burden in the world and in China and the United States has continued to decline, but China's disease burden is still significantly higher than the global average. The disease burden in men far exceeds that in women, with men and the population aged ≥50 years being high-risk groups. In the future, the global disease trend may reverse and rise, while China and the United States are expected to continuously decline. However, precise prevention and control for high-risk groups remains a key challenge.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

Objective:To investigate the correlation between expressions of serum procalcitonin (PCT), T-cell immunogloblin domain, mucin domain 4 (TIM-4) and prognosis of patients with severe pneumonia (SP) treated with bronchoalveolar lavage (BAL).Methods:Data of 497 patients with SP in the Department of Respiratory and Critical Care Medicine of the Affiliated Hospital of Yan'an University from June 2021 to June 2024 were retrospectively analyzed. Patients were divided into good prognosis group [pneumonia severity index (PSI) score<90 points, 289 cases] and poor prognosis group (PSI score≥90 points, 208 cases) according to the prognosis status of patients at 30 days after admission. The clinical data [history of smoking, alcohol consumption, history of hypertension, history of diabetes mellitus, gender, age, body mass index, PSI score after 30 d of admission, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and clinical pulmonary infection score (CPIS) after 14 days of treatment], serum PCT and TIM-4 levels were compared between both groups. Measurement data with normal distribution were expressed as xˉ± s, and t test was used for comparison between groups. Enumeration data were represented as n (%), and the composition ratio between groups was compared by χ2 test. The influencing factors of prognosis of BAL in the treatment of SP were analyzed by multivariate Logistic regression analysis. ROC curve was applied to analyze the diagnostic efficiency of serum PCT and TIM-4 on prognosis of BAL therapy. Results:Age (56.79±11.98) years, APACHEⅡscore (9.98±3.27) and CPIS score (6.54±1.81) in the good prognosis group were younger or lower than those in the poor prognosis group [(62.74±10.57) years, (13.06±4.25), (8.12±1.97)] ( t=5.734, 9.127, 9.250, respectively, P<0.001). The PCT (0.41±0.08) μg/L and TIM-4 (61.79±15.62) ng/L after treatment were higher in the poor prognosis group than those in the good prognosis group [(0.35±0.07) μg/L, (48.76±14.58) ng/L] ( t=8.876, 9.538, respectively, P<0.001). Multivariate Logistic regression analysis suggested that after excluding the interference effects of other factors, PCT ( OR=3.615, 95% CI: 1.641-7.964) and TIM-4 ( OR=4.047, 95% CI: 1.773-9.236) were influencing factors of prognosis in patients with SP receiving BAL therapy ( P=0.002, 0.001). ROC curve analysis indicated that the AUC value of PCT, TIM-4 and the combination of both in the diagnosis of prognosis of BAL therapy of SP were 0.782, 0.828 and 0.887 respectively, all of which had efficiency on predicting prognosis (all P<0.001). The sensitivity and specificity of combined prediction were 88.00% and 72.00%. Conclusion:The expressions of serum PCT and TIM-4 are closely related to the prognosis of SP patients receiving BAL. The PCT, TIM-4 and combination of both are of important reference value for prognosis prediction.

Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

OBJECTIVE: To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS). METHODS: A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children's Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). RESULTS: The infant was born prematurely at 35⁺³ weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c.1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. CONCLUSION This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c.1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.
Humans ; Serine Peptidase Inhibitor Kazal-Type 5/genetics* ; Netherton Syndrome/genetics* ; Female ; Infant, Newborn ; Infant, Premature ; Mutation ; Exome Sequencing ; Male

Objective To explore the application effect of constructing a data sharing-based multidrug-resistant or-ganism(MDRO)information reminder system combined with multidisciplinary standardized measures on the whole-process closed-loop management of MDRO.Methods Hospitalized patients from whom MDRO were detected from January 1 to July 31,2024 were taken as the control group,those from August 1,2024,to May 31,2025 were as the intervention group.The control group adopted the traditional manual reporting mode for MDRO,while the in-tervention group adopted the combination of MDRO reminder system and multidisciplinary management mode.Differences in isolation order issuing rate for MDRO and process-and outcome-indicators for multidisciplinary spe-cialty before and after system implementation were compared.Results After implementing information reminder system combined with multidisciplinary measures,issuing rates of ≤24 hour and＜4 hour MDRO isolation orders in the intervention group were both higher than in the control group([90.20％vs 65.23％,P＜0.05],[80.64％vs 55.08％,P＜0.001],respectively).Antimicrobial use rate in the intervention group was lower than in the con-trol group(36.27％vs 43.41％),with a statistically significant difference(P＜0.05).The implementation rates of MDRO prevention and control measures,pathogen detection rates,and fluorescence labeling clearance rates in the intervention group were all higher than those in the control group,all with statistically significant differences(all P＜0.05).The detection rate of MDRO decreased compared with the control group(10.83％vs 16.49％),and the in-cidence of MDRO healthcare-associated infection in the intervention group was lower than that in the control group(0.09％vs 0.19％),both with statistically significant differences(both P＜0.001).The treatment expense in the intervention group reduced by 27 422 Yuan compared with the control group.Conclusion This study constructed an MDRO reminder system,realized full-chain monitoring system for the multidisciplinary MDRO information interac-tion platform,strengthened multidisciplinary in-depth integration,and improved the prevention and control effect for MDRO.

Objective:To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS).Methods:A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children′s Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). Results:The infant was born prematurely at 35 + 3 weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c. 1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. Conclusion:This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c. 1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.

To investigate the effects ofS-Adenosylmethionine(SAM)on liver injury induced by carbon tetrachloride(CCl4)in mice,In this study,60 C57BL/6 mice were randomly divided into CON group,CCl4 group,low dose group(CCl4+SAM-L,50 mg/kg SAM),medium dose group(CCl4+SAM-M,100 mg/kg)and high dose group(CCl4+SAM-M,200 mg/kg).Except CON group,mice in other groups were intraperitoneally injected with CCl4(10 mL/kg,0.2％),and mice in CON group were injected with equal volume olive oil,3 times a week for 4 weeks,to establish mouse liver injury model.At the same time,mice in low,medium and high dose groups were given 100 μL SAM,CON group and CCl4 group were given equal volume PBS for 4 weeks.The results showed that CCl4 promoted liver fibrosis and increased serum ALT,AST and TBIL levels(P＜0.05).Different doses of SAM significantly alleviated liver fibrosis injury and decreased serum ALT,AST and TBIL levels(P＜0.05).Compared with CON group,CCl4 significantly decreased the liver T-AOC,SOD,CAT and GSH-Px levels(P＜0.05),and increased the liver MDA level(P＜0.05).Compared with CCl4 group,the levels of T-AOC,SOD,CAT and GSH-PX in liver of mice in CCl4+SAM group were significantly increased(P＜0.05),while the level of MDA was significantly decreased(P＜0.05).Compared with CON group,liver levels of IL-6,IL-1β and TNF-α in CCl4 group were significantly increased(P＜0.05).Compared with CCl4 group,different doses of SAM could significantly reduce the levels of IL-6,IL-1β and TNF-α in liver of mice(P＜0.05).Compared with CON group,the expressions of Nrf2,NQO-1 and HO-1 genes in liver of CCl4 group were decreased(P＞0.05),while the expression of Keap1 gene was significantly increased(P＞0.05).Compared with CCl4 group,medium and high doses of SAM significantly increased the expressions of Nrf2,NQO-1 and HO-1 genes in liver of mice(P＜0.05),and decreased the expres-sion of Keap1 gene(P＞0.05).Compared with CON group,the contents of acetic acid,propionic acid and butyric acid in cecum of CCl4 group were significantly decreased(P＜0.05).Compared with CCl4 group,the contents of propionic acid and butyric acid in high-dose SAM group were sig-nificantly increased(P＜0.05).Microbial analysis showed that CCl4 significantly decreased the rel-ative abundance of Akkermansia and Prevotellaceae_NK3B31_group(P＜0.05),and changed the composition of intestinal microorganisms.These results indicate that SAM regulates the gene ex-pression of Nrf2 antioxidant signaling pathway to a certain extent,increases intestinal SCFAs con-tent,regulates intestinal microbial structure,and thus alleviates liver injury,oxidative stress and inflammation caused by CCl4.This study provides reference and theoretical basis for SAM in the treatment and remission of drug-induced liver injury.

In recent years, the bacteriophage Φ29 (Phi29) DNA polymerase has garnered increasing attention due to its high-fidelity amplification capacity at constant temperatures. To advance the industrial application of this type of isothermal polymerases, this study mined and characterized new enzymes from the microbial metagenome based on the known Phi29 DNA polymerase sequence. The results revealed that a new enzyme, Php29 DNA polymerase, was identified in the microbial metagenome with plants as the hosts. This enzyme exhibited higher strand displacement activity, with a 59.5% similarity to bacteriophage Φ29. Experimental validation demonstrated that the enzyme had 3'→5' exonuclease activity, and its amplification products can serve as substrates for further catalytic reactions. The discovery and validation of Php29 DNA polymerase gives insights into the future industrial application of isothermal polymerases.
DNA-Directed DNA Polymerase/metabolism* ; Bacillus Phages/genetics* ; Metagenome